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The cybersecurity threat landscape evolves quickly, continually, and consequentially. This means that the "transfer" of cybersecurity learning is crucial. We compared how different recognized "cognitive" transfer theories might help explain and synergize three aspects of cybersecurity education. These include "teaching and training" in diverse settings, "assessing learning" formatively & summatively, and "testing & measuring" achievement, proficiency, & readiness. We excluded newer sociocultural theories and their implications for inclusion as we explore those theories elsewhere. We first summarized the history of cybersecurity education and proficiency standards considering transfer theories. We then explored each theory and reviewed the most relevant cybersecurity education research; in some cases, we broadened our search to computing education. We concluded that (a) archaic "differential" transfer theories are still influential but have negative implications to be avoided, (b) "constructionist" theories are popular in K-12 settings but raise issues for assessment and transfer, (c) many embrace a "general cognitive science perspective" that can resolve tensions between modern "cognitive-associationist" and "cognitive-constructivist" theories that are popular with innovators, and (d) new "perceptual" and "coordinative" theories have potential worth exploring. These insights should support "generative" cybersecurity learning that transfers readily and widely to future classes, tests, and workplaces. These insights should be beneficial when designing and using cyber "ranges" and other hyper-realistic simulations, where transfer assumptions inform costly design decisions and undergird the validity of performance as evidence of proficiency.

Teen dating violence (TDV) is a significant public health problem that can have lifelong consequences. Using a longitudinal, cluster randomized controlled trial (RCT), this study examines whether the "Dating Matters" comprehensive prevention model, implemented in middle school, prevented TDV and negative relationship behaviors and promoted positive relationship behaviors in high school (9th-11th grades), when compared with a standard of care intervention. "Dating Matters" includes programs for sixth to eighth grade youth and their parents, training for school staff, a youth communications program, and policy and data activities implemented in the community. Self-report survey data were collected from students in 46 middle schools that were randomly assigned to condition within site. Students completed two surveys (fall and spring) in each middle school grade and a single survey in the spring of each high school grade. This study examined self-reported TDV perpetration and victimization, use of negative conflict resolution strategies, and positive relationship skills in the high school follow-up. While varying patterns emerged, latent panel models demonstrated significant program effects for all outcomes. "Dating Matters" students reported 19% reduced risk for TDV perpetration, 24% reduced risk for TDV victimization, 7% reduced risk for use of negative conflict strategies, and 3% more use of positive relationship skills, on average across time and cohort, than standard of care students. On average, "Dating Matters," implemented in middle school, continued to be more effective at reducing TDV perpetration, TDV victimization, and use of negative conflict resolution strategies in high school than an evidence-based comparison program.

Marie Ociskova,1,2 Jan Prasko,1– 4 Krystof Kantor,1,5 Jakub Vanek,1 Vlastimil Nesnidal,1 Kamila Belohradova1 1Department of Psychiatry, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic; 2Jessenia Inc. Rehabilitation Hospital Beroun, Akeso Holding, MINDWALK, S.r.o, Beroun, Czech Republic; 3Department of Psychological Sciences, Faculty of Social Sciences and Health Care, Constantine the Philosopher University in Nitra, Nitra, Slovak Republic; 4Department of Psychotherapy, Institute for Postgraduate Training in Health Care, Prague, Czech Republic; 5Department of Child Psychiatry, University Hospital in Motol, Prague, Czech RepublicCorrespondence: Jan Prasko, Department of Psychiatry, Faculty of Medicine and Dentistry, Palacky University in Olomouc, Hnevotinska 3, Olomouc, 779 00, Czech Republic, Email praskojan@seznam.czPurpose: Child abuse and trauma are significant risk factors in the etiology of borderline personality disorder (BPD). Apart from affecting the risk of developing BPD, adverse childhood experiences seem to increase its symptoms and related disability. Self-stigma presents another common issue with equally prominent consequences for mental health. Despite being theoretically linked, the connections among childhood trauma, self-stigma, and mental health have not been explored in patients with BPD. This study aimed to provide first insights into this understudied topic.Patients and Methods: This cross-sectional study included 283 inpatients diagnosed with BPD participating in a residential transdiagnostic psychotherapeutic program. The patients completed several measurements – the Internalized Stigma of Mental Illness Scale, the Childhood Trauma Questionnaire – Short Form, the Clinical Global Impression – Severity, the Beck Depression Inventory-II, the Beck Anxiety Inventory, the Dissociative Experiences Scale, the Sheehan Disability Scale, and a demographic questionnaire. The data was statistically analyzed using IBM SPSS and AMOS 26 programs, and bivariate correlation tests and structural equation modeling explored the hypotheses.Results: Retrospectively reported childhood trauma positively correlated with current self-stigma. Both childhood trauma and self-stigma were also positively related to several indicators of general psychopathology and disability. The significance of these connections was subsequently confirmed by structural equation modeling, where self-stigma acted as a partial mediator of childhood trauma, general psychopathology, and disability.Conclusion: Self-stigma significantly mediates the relationship between childhood trauma and selected mental health symptoms among adult patients diagnosed with BPD. Longitudinal studies are necessary to explore the causality of the findings. Therapeutic and societal efforts to tackle childhood trauma or self-stigma might benefit from reflecting its broader psychosocial context.Keywords: borderline personality disorder, self-stigma, childhood trauma, depression, anxiety, disability

Abstract Background Despite evidence demonstrating the effectiveness of the COVID-19 vaccine, vaccine hesitancy has emerged as a major challenge for vaccine uptake. The objective of this study was to classify latent typologies of vaccine hesitant adults in Ethiopia and identify predictors of the latent classes. Methods We employed a cross-sectional household survey among 1,112 individuals aged 18 and above who were partially vaccinated (one dose) or not vaccinated at the time of the survey. Data was collected in August 2022. We collected information on participant socio-demographics, COVID-19 knowledge, prevention practices, disease history, and vaccine hesitancy. Latent class analysis was used to classify individuals into categories of vaccine hesitancy. We conducted multinomial logistic regression to test the associations between latent typologies and different demographic and COVID-19 related characteristics of study participants. Results Using latent class analysis we found a four-class solution for vaccine hesitancy typologies. The identified classes were strong vaccine acceptors (30%); vaccine acceptors with some concerns (7%); vaccine sceptics (13%); and vaccine rejectors (50%). In adjusted models with vaccine sceptics as the referent group, those with high COVID-19 vaccine knowledge were significantly more likely to belong to the strong vaccine acceptors class compared to those with low vaccine knowledge (adj. RRR: 17.36, 95% CI: 10.94–27.55). Better COVID-19 prevention practices were also significantly associated with belonging to the vaccine acceptors with some concerns class than the vaccine sceptics class (adj. RRR: 2.13, 95% CI: 1.09–4.16). Those who had one dose of the COVID-19 vaccine were significantly more likely to belong in the vaccine acceptors class than the vaccine sceptics class compared to those who had no dose (adj. RRR: 6.82, 95% CI: 3.06–15.21). Conclusions Half of the study participants were in the vaccine rejectors class. Individuals in the vaccine sceptics and rejector classes evidenced lower vaccine knowledge and worse COVD-19 prevention practices and were less likely to have been partially vaccinated. Future program interventions should focus on improving knowledge around the vaccine, decrease rumors and misconceptions, and target individuals who may be more amenable to changing their vaccination attitudes or behaviors like vaccine sceptics or acceptors with some concerns.

Abstract Despite extensive evidence on the impact of various mental health issues including smartphone/internet addiction, and personality traits on academic achievement, little is known about the complex interactions between multiple of these factors simultaneously, as well as cross-country differences in these nuanced relationships. In particular, understanding the role of the mentioned addictions has become increasingly important in recent years in the context of the COVID-19 pandemic. The aim of this cross-country study was to investigate, using path analysis, the complex relationships between mental health determinants (depression, anxiety, stress, resilience, and smartphone/internet addiction) and academic achievement in 1785 Czech and Chinese university students using an online battery of psychological tests. The results confirmed the previously described effect of multiple factors (anxiety, stress, resilience, smartphone/internet addiction, personality traits, and sex, Extraversion, Agreeableness, Conscientiousness) on academic achievement, overlapping in most cases for both groups of students. At the same time, however, different country-dependent patterns of interactions emerged. For the Czech students, the variables formed a complex network of interacting factors, whereas for the Chinese students, the effect of each cluster of factors was separate for individual domains of academic achievement. These cross-country differences have implications particularly for planning and targeting the most effective interventions to promote and develop academic achievement.

Background: MicroRNAs (miRNAs) show promise as blood-based tumor markers for germ cell tumors (GCTs), with miRNA-371-3p being the most studied. The marginal benefit of including other candidate miRNAs to aid with the management of testicular GCTs remains unclear. Objective: To assess the performance of our combined miRNA assay (371a-3p and 372-3p) in patients with clinically localized testicular masses. Design, setting, and participants: This was a retrospective review of patients prospectively enrolled in an ongoing protocol collecting serum miR-371a-3p and miR-372-3p levels (together, Memorial Sloan Kettering Cancer Center [MSK] miRNA assay [MMA]) in patients with a suspected or diagnosed testicular GCT. Outcome measurements and statistical analysis: The coprimary outcomes of interest were sensitivity and specificity of miR-371a-3p and 372-3p, individually and together, to detect nonteratomatous GCTs in the orchiectomy specimen. Secondary outcomes included additional assay diagnostic parameters, the relationship of patient and disease factors with variations in miRNA levels, and temporal patterns of miRNA normalization after orchiectomy. Results and limitations: Sixty-two patients were included, 52 had a viable GCT at orchiectomy, and ten had no cancer or a non-GCT. Forty-six patients with a GCT had positive preorchiectomy MMA (sensitivity 88.5% [95% confidence interval {CI}: 79.8, 97.2]), and one patient had positive preorchiectomy MMA but no GCT (specificity 90.0% [95% CI: 71.4, 100]). The diagnostic performance of miR-371a-3-p and miR-372-3p was similar. The time for miRNA to decrease to undetectable levels varied, with some patients having positive levels up to 3 wk after orchiectomy. Conclusions: The biomarkers miR-371a-3p and miR-372-3p demonstrated high sensitivity and specificity for localized testicular GCTs, but causes of variation in relative miRNA levels and time to normalization for individual patients remain unclear. Patient summary: We studied the ability of the blood-based biomarkers miR-371a-3p and miR-372-3p to detect testicular cancer (germ cell tumors) in patients with small testicular masses. We found that together and individually these were sensitive and specific for testicular cancer.

Abstract Fe1-x O, although chemically simple, possesses a complex structural and magnetic phase diagram. The crystal structures of Fe1-x O and its magnetic properties at extreme conditions are still a matter of debate. Here, we performed a systematic investigation on Fe0.94O up to 94 GPa and 1700 K using synchrotron X-ray diffraction and synchrotron Mössbauer source spectroscopy. We observe a transition of Fe0.94O to the monoclinic phases above 40 GPa and at high temperatures and use the group theory analysis of the observed phases to discuss their properties and their relation to the ambient pressure phases. The Mössbauer spectra of the rhombohedral and the room temperature monoclinic phase contain a component attributed to Fe2.5+, caused by the electron exchange between the Fe3+ defect and neighboring Fe2+ atoms. Our results present a structural and magnetic transitional pressure-temperature diagram of Fe1-x O and show the complex physicochemical properties of simple Fe1-x O binary oxide under extreme conditions.

Introduction. Diversification of education of children with special needs, carried out on the basis of the inclusive educational paradigm, actualized the tasks of formation and development of inclusive competencies of teachers in general educational organizations. These competencies, however, should be considered in their connection with inclusive dispositions of a teacher as meaning structures of his/her personality. But the problem of interrelation of inclusive dispositions and teachers’ competences has not been empirically developed so far. Establishing the nature of the relationship between inclusive dispositions and competences of teachers of general education organizations was the purpose of the study, which was implemented in the context of the typological approach to inclusive dispositions of teachers and the materials of which are presented in the paper. Materials and Methods. The study surveyed 759 primary, secondary, and supplementary education teachers from 7 federal districts of Russia. The authors employed diagnostic methods, including a situational professional test for evaluating the development of inclusive competencies in teachers, as well as a self-identification questionnaire for determining a teacher’s inclusive dispositions. Results. The materials of the study show that there are reliable differences between teachers characterized by different types of inclusive dispositions with regard to all basic inclusive competencies. Least of all they are formed among teachers with pronounced negative and skeptical inclusive dispositions, with the negative disposition acting as a predictor of underdevelopment of teachers’ inclusive competencies, while the links of supportive and analytical inclusive dispositions with teachers’ inclusive competencies are weak, although reliable. Discussion and Conclusion. The study, augmented by newly obtained empirical data, enhances understanding of the professional and personal readiness of teachers for inclusive education. Its findings underscore the necessity of focused efforts to shape and refine the perceptions of a teacher’s professional activities within inclusive settings. This necessitates their integration into the development of professional training programs geared towards inclusion for teachers.

Background: Dermatology journals play an essential role in the distribution and promotion of scientific and medical information. Despite this, there are little data on governance structure with respect to its editors, owners, and journal boards that oversee the day-to-day operations for these entities. Objective: This study aimed to explore the current governance structure of dermatology journals and best practice recommendations. Methods: The editors-in-chief of the major dermatology journals participated in an online survey of 29 questions to examine general statistics of each journal, open access model, governance structure, and process for editor selection or dismissal. Results: Of the 52 journal responses, 29 (55.8%) are society-owned journals with 19 (65.5%) primarily governed by a society board, while 18 (34.6%) have an advisory committee or alternative body. Most editor(s)-in-chief (56.9%) serve between 3- and 5-year terms, while 84.6% have the option of at least one renewal. Even though the selection, evaluation, and dismissal processes differed between the journals, generalized best practice recommendations were developed to help improve their overall organization and management. Conclusions: The oversight structure of dermatology journals varies, and some do not follow current best practice recommendations. Transparency regarding leadership, governance, and due process is needed to maintain editorial independence and integrity.

The article again addresses the issue of forensic examinations of incapacity or limited capacity due to the mental disorder in the Code of Civil Procedure of the Russian Federation. The article critically discusses the common objections to establishing a mandatory appointment for a comprehensive forensic psychological and psychiatric examination in this category of cases. The author observes how this proposed requirement is connected with earlier legislation updates. The new rule logically follows from the need to consider, in according to law, a person’s ability for decision making and social communication. Currently, a comprehensive forensic psychological and psychiatric examination is appointed too rarely in these cases, which leads to the insufficient comprehension of these significant factors by the courts. Organizational and technical hurdles, which are considered to be main arguments against the discussed rule, shouldn’t prevent the long overdue legislation innovations. Statistical data presented by the opponents relates to different categories of cases and, therefore, cannot be a basis for the conclusions about the issue discussed.

This study describes the case of a student with congenital intestinal perforations and her experience with inclusive education in the Czech Republic. She is also a sister of an identical twin with cerebral palsy. The data were gained from semi-structured interviews and bio-graphical narratives of the student during her studies at the grammar school and from her parents. Van Manen's analyses of lived experiences was used to identify important themes for each participant. The overarching themes present in their narratives concerned Lucy's future and the choice of the most appropriate educational environment. The parents' narratives focused more on barriers to inclusive education, benefits of inclusive environments, medical and educational care and family support based on close cooperation with school. For Lucy, the dominant theme was being a sister with a less severe disability and caretaking of her sister. In addition to enhancing the understanding of different needs of a student with congenital malformations and her parents' experiences with inclusive education, it helped us to explore how the specific sibling's constellation within her family and school contexts impacts her personal perspective on life, driven strongly by a wish for independence.

Long-term water uptake of Douglas-fir and Norway spruce trees, growing in condition of Moravian upland, was studied with aim of comparing sap flow in small roots with flow in stems. Sap flow was measured by the heat field deformation method using multi-point sensors for stems and single-point sensors for roots. Differences between species were found in relationships between sap flow in tree stems and water uptake by roots, suggesting that Douglas-fir is able to take water from deeper soil more efficiently than spruce. This allows Douglas-fir to transpire more water especially during drought and grow faster than spruce. These biological features should be taken into account for future forest species compositions because they may have impact on both, forestry and hydrology.

Abstract Safely and efficiently controlling gene expression is a long-standing goal of biomedical research, and CRISPR/Cas system can be harnessed to create powerful tools for epigenetic editing. Adeno-associated-viruses (AAVs) represent the delivery vehicle of choice for therapeutic platform. However, their small packaging capacity isn’t suitable for large constructs including most CRISPR/dCas9-effector vectors. Thus, AAV-based CRISPR/Cas systems have been delivered via two separate viral vectors. Here we develop a compact CRISPR/dCas9-based repressor system packaged in AAV as a single optimized vector. The system comprises the small Staphylococcus aureus (Sa)dCas9 and an engineered repressor molecule, a fusion of MeCP2’s transcription repression domain (TRD) and KRAB. The dSaCas9-KRAB-MeCP2(TRD) vector platform repressed robustly and sustainably the expression of multiple genes-of-interest, in vitro and in vivo, including ApoE, the strongest genetic risk factor for late onset Alzheimer’s disease (LOAD). Our platform broadens the CRISPR/dCas9 toolset available for transcriptional manipulation of gene expression in research and therapeutic settings.

Aim of the study This qualitative study explores the resilience of medical staff working in emergency units during the COVID-19 pandemic. Through in-depth interviews and thematic analysis, the research investigates how frontline healthcare workers coped with unprecedented challenges. Key themes identified include professional commitment, teamwork, and adaptability, which were crucial in navigating the crisis. Materials and methods: In order to assess the resilience of the medical staff in the COVID-19 pandemic between March 1, 2022 and March 31, 2021, a study was conducted in three emergency units in Romania: County Hospital of Emergency „Saint Spiridon” Iassy, Emergency University Hospital Bucharest and County Hospital of Emergency “Saint John the New” Suceava. Results: The study highlights the significant emotional and psychological toll on medical staff and underscores the importance of institutional support systems. Findings suggest that enhancing resilience through training, mental health resources, and robust communication channels is essential for future preparedness. Conclusions: This research provides valuable insights into the experiences of healthcare workers and emphasizes the need for sustained support to ensure the well-being and efficacy of medical personnel in emergency settings.

Objectives: Time-to-treatment initiation is an important consideration for patients undergoing thoracic surgery for early-stage lung cancer because delays have the potential to adversely affect outcomes. This study seeks to quantify time-to-treatment initiation for patients with clinical stage I lung cancer, explore patient factors and predictors that lead to an increased time-to-treatment initiation, and compare surgeon perception of appropriate time-to-treatment initiation to the results. Methods: Time-to-treatment initiation was determined for patients enrolled in the Mount Sinai Initiative for Early Lung Cancer Research on Treatment study who underwent surgical resection for clinical stage I lung cancer between March 2016 and December 2021. The following dates were determined: (1) date of first suspicious radiologic imaging, (2) date of first biopsy, and (3) date of surgery. A total of 15 thoracic surgeons who participated in the Mount Sinai Initiative for Early Lung Cancer Research on Treatment were assessed on their perception on time-to-treatment initiation. Results: For 638 patients, median time from first suspicious imaging findings to biopsy was 40 days, biopsy to surgery was 37 days, and suspicious imaging to surgery was 84 days. Significant factors that resulted in longer time-to-treatment initiation in the multivariate analysis were African American or Black race (P = .005), vascular disease (P = .01), and median household income less than $75,000 (P = .04). Although the surgeon's perception was that the average time from biopsy to surgery was 28 days, it was longer for 63.5% of participants; surgeon perception of maximum time between diagnosis and surgery was 84 days and longer for 28.7% of participants. Conclusions: Patient factors such as race, income, and comorbidities were found to have differences in time-to-treatment initiation. Delays to surgery exceeded the expectations of thoracic surgeons.

Abstract Background Little is known about how use of chemotherapy has evolved in breast cancer patients. We therefore describe chemotherapy patterns for women with stage I-IIIA breast cancer in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) Study using data from KPNC (Kaiser Permanente Northern California) and KPWA (Kaiser Permanente Washington). Findings Among 33,670 women, aged 18 + y, diagnosed with primary stage I-IIIA breast cancer at KPNC and KPWA from 2006 to 2019, we explored patterns of intravenous chemotherapy use, defined here as receipt of intravenous cytotoxic drugs and/or anti-HER2 therapies. We evaluated trends in chemotherapy receipt, duration over which chemotherapy was received, and number of associated infusion visits. In secondary analyses, we stratified by receipt of anti-HER2 therapies (trastuzumab and/or pertuzumab), given their longer duration. 38.9% received chemotherapy intravenously, declining from 40.2% in 2006 to 35.6% in 2019 (p-trend

Introduction: The Radical Remission Multimodal Intervention (RRMI) was developed by Kelly A. Turner, PhD, after analyzing more than 1500 cases of cancer survivors experiencing radical remission (a.k.a. spontaneous regression) across all cancer types and extracting key lifestyle factors shared by these cancer survivors. The RRMI workshops provide instruction on these lifestyle factors to participants with cancer and give them tools to help navigate their cancer recovery journey. This pilot study aimed to evaluate the effect of the RRMI on the quality of life (QOL) of people with cancer. Methods: This was a pre-post outcome study. Data were collected, between January 2019 and January 2022, from 200 eligible adults of all cancer types, who attended the RRMI workshops (online and in-person). Participants were asked to complete questionnaires online, at baseline (i.e., before the intervention) and at month 1 and month 6 post-intervention. The RRMI workshops were led by certified Radical Remission health coaches. Participants completed the RRMI with personalized action plans for them to implement. The primary outcome QOL measure was the Functional Assessment of Chronic Illness Therapy—Spiritual Well-Being Scale (FACIT-Sp). Mixed-effects regression models were used to examine differences in FACIT-Sp score between month 1 and baseline, as well as month 6 and baseline. Models controlled for baseline score, covariates (including age, ethnic group, and body mass index), timepoints (month 1 or 6), training type (online or in-person), adherence score, and interaction between timepoints and adherence score. Results: 92% of participants were women, 77% were Non-Hispanic White, 88% were living in the US, and 66.5% were not living alone. One-quarter had breast cancer. Mean age ± SD was 55.3 ± 11.5 years. Final mixed-effects model analyses showed a significant increase in FACIT-Sp score of 9.5 (95% confidence interval [CI]: 6.2-12.8) points at month 1 ( P

Introduction and objective Endometriosis is a complex systemic condition characterized by the growth of functional endometrial tissue outside the uterine cavity, affecting 10-15% of women of reproductive age. Up to 50% of these women face infertility challenges. Although there is a scientifically established connection between endometriosis and infertility, the underlying mechanisms remain not fully understood. Review methods The PubMed database was searched using phrases related to the topic of endometriosis-associated infertility. The search included original research articles, review papers, and guidelines, including the Polish guideline on managing women with endometriosis. Ultimately, 25 relevant sources presenting the latest knowledge were selected. Abbreviated description of the state of knowledge The pathogenesis of infertility associated with endometriosis is complex and involves multiple factors. The most frequently cited contributors in the scientific literature include pain and dyspareunia, mechanical factors, reduced ovarian reserve, oxidative stress, changes in embryo and oocyte quality, impaired ovulation, and compromised endometrial receptivity. Summary Endometriosis affects a growing number of women worldwide, with nearly half experiencing infertility. The complexity and involvement of multiple organ systems make it difficult to pinpoint a single cause, posing a challenge for clinicians. Addressing these diverse factors is essential for improving fertility management in women with endometriosis.

Introduction and objective. Receiving a cancer diagnosis can lead to significant mental distress, highlighting the necessity for comprehensive medical care that includes psychological support. Effective psycho-oncological therapy can help patients find fulfillment regardless of their prognosis, while also improving overall outcomes and treatment adherence. This article aims to review the medical literature on the mental health challenges faced by cancer patients and to explore potential treatment modalities. Review methods. Implementing Google Scholar and PubMed, a literature analysis was conducted, with particular attention paid to terms like "psychooncology," "anxiety," "depression," "cancer," "grief," and "PTSD." The period of consideration for articles was from 2017 to 2024. Brief description of the state of knowledge. Grief, anxiety, PTSD, despair, and other mental health problems can arise after receiving a cancer diagnosis. In order to improve treatment adherence and survival rates, psychological well-being must be addressed. Empirical evidence indicates that psychological disorders can hinder adherence to therapy and elevate the risk of death from cancer. Furthermore, as families often endure significant stress throughout the disease, psychological care is beneficial to both patients and their relatives. It is possible to enhance adherence and reduce symptoms by using an integrated strategy that takes into consideration both physical and mental health. Conclusions. An essential part of holistic cancer care is psycho-oncology, which enhances patients' general health and quality of life. Psycho-oncological therapy must be incorporated into standard cancer care in order to improve treatment outcomes and assist patients in overcoming their condition.

CRC occupies one of the leading positions among gastrointestinal malignancies and is a significant problem in Europe since it is the third most frequently diagnosed cancer. Recent developments in diagnostic techniques have led to higher chances of early diagnosis and survival; nevertheless, CRC is highly likely to relapse in the survivorably younger individuals. The importance of the current chemotherapy treatment and potential key therapeutic targets are identified in this review so that the molecular alterations causing drug resistance in CRC can be studied.Current literature formed the basis of this review by reviewing the molecular processes that underlie CRC, with emphasis on the mutational alterations in genes such as SENP1, KRAS, APC, TP53, and BRAF that play critical roles in CRC and resistance to treatment. Chemotherapy for CRC, targeting therapies, and immuno therapies have been discussed particularly with reference to their effectiveness for treatment and overcoming resistance.Genomic alterations in some important genes are involved in the onset of CRC and also determined the response to therapies. The KRAS mutations are associated with the resistance to EGFR inhibitors; however, BRAF mutations require BRAF/MEK inhibitors. Lack of MMR system SSR as a trigger for MSI-H status suggests a better response to immunotherapies. In addition, new molecules including SENP1, which involved the DNA repair pathway, and combination using CDK4/6 inhibitors are currently under development to overcome resistance and enhance the patients’ benefits.Colorectal cancer is still a problem, primarily because of its genetic character and high rates of recurrence. Even though chemotherapy and targeted therapies offer helpful results, the problem of resistance stands in the way. Subsequent studies should aim at symptomatic treatment outcomes and combine different drugs in order to enhance long-term treatment outcomes.

На основі узагальнення основних утвердже­них в українській науці адміністративного права точок зору на склад та спрямованість завдань адміністративного права автор визначив, що їх об’єднує визнання завданнями адміністратив­ного права: 1) конкретизацію та забезпечення реалізації прав і свобод людини у публічно-пра­вовій площині шляхом упровадження механіз­мів адміністративно-правового регулювання та охорони у сфері публічного адміністрування; 2) визначення стандартів здійснення суб’єктами владних повноважень публічно-владних управ­лінських функцій та надання ними адміністра­тивних послуг, а також установлення й вдоско­наленняматеріально-правового та процедурно­го інструментарію діяльності суб’єктів владних повноважень, у тому числі, засобів правового захисту від порушень з їх боку, механізмів гро­мадянського контролю за їх діяльністю. За підсумками дослідження прикладів розу­міння завдань адміністративного права у зару­біжній науковій думці, у статті зауважено, що згідно з національною традицією держав з пра­вовою системою загального права, яка була перейнята багатьма державами, які представ­ляють правову сім’ю континентального права, основоположним завданням адміністративно­го права визнається визначення оптимальних з точки зору верховенства права та ефектив­ності публічного адміністрування меж свобо­ди управлінського розсуду суб’єктів владних повноважень та забезпечення приватних осіб засобами правового захисту від зловживань адміністративною владою. Також, помітним у вищевикладених формулюваннях завдань ад­міністративного права є особливий наголос на гарантуванні прозорості та підзвітності суб’єктів владних повноважень, насамперед, перед гро­мадянським суспільством. Менше значення має завдання адміністративного права, що полягає у встановленні принципів, матеріально-право­вих правил та процедури виконання владних управлінських функцій адміністративними орга­нами, а також накопичення у адміністративній та судовій практиці потенціалу для підвищення ефективності адміністративного права.

Objectives To describe the development, validation and reliability of the Oxford Vaccine Hesitancy Scale (OVHS), a new instrument to assess vaccine hesitancy in the general population.Design Cross-sectional validation study.Setting Internet-based study with participants in the UK and USA.Participants Demographically representative (stratified by age, sex and race) samples from the UK and USA recruited through the Prolific Academic platform.Main outcome measures To demonstrate OVHS development, exploratory factor analysis with categorical variables and a polychoric correlation matrix followed by promax oblique rotation on the UK sample was performed. Confirmatory factor analysis with a Satorra-Bentler scaled test statistic evaluating goodness of fit statistics including the root mean squared error of approximation (RMSEA), standardised root mean squared residual (SRMR) and comparative fit index (CFI) was performed on the US sample. Reliability as internal consistency was assessed using McDonald’s omega. Evidence in support of the predictive, convergent and discriminant validity of the scale was assessed using logistic regression ORs of association (OR) or Pearson correlation coefficients.Results Data for factor analysis were obtained from 1004 respondents, 504 in the UK and 500 in the USA. A scree plot, minimum average partial correlation analysis and parallel analysis suggested a three-factor 13-item scale with domains of vaccine beliefs (seven items), pain (three items) and personal deliberation (three items). Responses were recorded on a Likert scale ranging from disagree completely to agree completely, with higher score reflecting greater hesitancy. Potential total scores ranged from 13 to 65. Goodness of fit was excellent, with RMSEA=0.044, SRMR=0.041 and CFI=0.977. Predictive validity for COVID-19 vaccination status was excellent, with logistic regression ORs of association (95% CI) of 0.07 (0.04, 0.13), p

Abstract Sarcopenia is a serious systemic disease that reduces overall survival. TAVI is selectively performed in patients with severe aortic stenosis who are not indicated for open cardiac surgery due to severe polymorbidity. Artificial intelligence-assisted body composition assessment from available CT scans appears to be a simple tool to stratify these patients into low and high risk based on future estimates of all-cause mortality. Within our study, the segmentation of preprocedural CT scans at the level of the lumbar third vertebra in patients undergoing TAVI was performed using a neural network (AutoMATiCA). The obtained parameters (area and density of skeletal muscles and intramuscular, visceral, and subcutaneous adipose tissue) were analyzed using Cox univariate and multivariable models for continuous and categorical variables to assess the relation of selected variables with all-cause mortality. 866 patients were included (median(interquartile range)): age 79.7 (74.9–83.3) years; BMI 28.9 (25.9–32.6) kg/m2. Survival analysis was performed on all automatically obtained parameters of muscle and fat density and area. Skeletal muscle index (SMI in cm2/m2), visceral (VAT in HU) and subcutaneous adipose tissue (SAT in HU) density predicted the all-cause mortality in patients after TAVI expressed as hazard ratio (HR) with 95% confidence interval (CI): SMI HR 0.986, 95% CI (0.975–0.996); VAT 1.015 (1.002–1.028) and SAT 1.014 (1.004–1.023), all p